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Hepatic encephalopathy

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Liver failure article more useful, or one of our other health articles.

See also the separate Liver Failure, Cirrhosis and Hepatorenal Syndrome articles.

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What is hepatic encephalopathy?

Hepatic encephalopathy is defined as a spectrum of neuropsychiatric abnormalities in patients with liver failure, after exclusion of other known brain disease. Hepatic encephalopathy can be subdivided into covert hepatic encephalopathy and overt hepatic encephalopathy.

Covert hepatic encephalopathy is a subclinical, less severe manifestation of hepatic encephalopathy and requires psychometric testing for diagnosis1 . Covert hepatic encephalopathy has a significant impact on a patient's quality of life, including employment and driving performance, and is associated with increased admissions to hospital and with death2 .

Features of hepatic encephalopathy include personality changes, intellectual impairment and reduced levels of consciousness. The pathogenesis of hepatic encephalopathy is uncertain but may be due to the passage of neurotoxins to the brain3 . Hepatic encephalopathy develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis4 .

Common precipitants

  • Acute kidney injury.

  • Electrolyte imbalance.

  • Gastrointestinal bleeding.

  • Infection.

  • Constipation.

  • Sedative drugs - eg, opiates, benzodiazepines, antidepressants and antipsychotic drugs.

  • Diuretics.

  • High protein intake.

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Hepatic encephalopathy symptoms (presentation)

Grading of hepatic encephalopathy5

  • Grade 0: subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, co-ordination. This is also termed minimal hepatic encephalopathy.

  • Grade 1: mild confusion, euphoria or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern such as inverted sleep cycle.

  • Grade 2: drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation.

  • Grade 3: somnolent but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, speech present but incomprehensible.

  • Grade 4: coma, with or without response to painful stimuli.

  • Patients with very mild hepatic encephalopathy may have normal memory, language and motor skills but may have impairment of attention and decision-making and may have impaired fitness to drive. These patients usually have normal function on standard mental state testing but abnormal psychometric testing.

  • Patients with mild and moderate hepatic encephalopathy show decreased short-term memory and concentration with testing of mental state. They may also have a flapping tremor (asterixis), fetor hepaticus (a sweet musty aroma of the breath), hyperventilation and hypothermia.

West Haven Criteria6

Since the above grading system was developed - in 1998 by a World Congress of Gastroenterology working party - the West Haven Criteria was published. These have become the standard criteria to assist in the diagnosis of hepatic encephalopathy:

Grade 1

  • Trivial lack of awareness.

  • Euphoria or anxiety.

  • Shortened attention span; impaired performance of addition or subtraction.

Grade 2

  • Lethargy or apathy.

  • Minimal disorientation for time or place.

  • Subtle personality change.

  • Inappropriate behaviour.

Grade 3

  • Somnolence to semi-stupor, but responsive to verbal stimuli.

  • Confusion.

  • Gross disorientation.

Grade 4

  • Coma.


  • Psychometric tests - this are becoming increasingly useful in the diagnosis of minimal hepatic encephalopathy.

  • Arterial or serum ammonia levels are raised and can help with diagnosis.

  • Electroencephalogram (EEG): may show high-amplitude low-frequency waves and triphasic waves but these findings are not specific for hepatic encephalopathy.

  • MRI/CT scanning can help to exclude other causes of altered mental function such as intracranial lesions.

  • Visual evoked responses show classic patterns associated with hepatic encephalopathy.

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Differential diagnosis

Other causes of encephalopathy, including:

Hepatic encephalopathy treatment and management

  • Early diagnosis and aggressive identification and management of precipitating factors7 .

  • Antibiotics (eg, rifaximin, neomycin/paromomycin/metronidazole, or vancomycin) are often given empirically as infection is a common underlying cause.

  • Methods to combat raised levels of ammonia. Lactulose/lactitol (a non-absorbable osmotic laxative that also helps convert ammonia to non-absorbable ammonium in the gastrointestinal tract), LOLA L-ornithine and L-aspartate preparation - increases the use of ammonia in the urea cycle to produce urea).

  • Sedative drugs should be avoided

Restriction of protein intake was once thought to be beneficial, but this was not supported by further evidence. Adequate nutrition is essential; in cirrhosis, there is actually an increased requirement for protein8 .

Drug treatment

  • The nitrogen load from the gut should be reduced using lactulose or bowel enemas9 . However, a systematic review found that there is insufficient evidence to support or refute the use of non-absorbable disaccharides for hepatic encephalopathy10 .

  • Antibiotics - eg, rifaximin, neomycin/paromomycin/metronidazole, or vancomycin - are often given empirically on the basis of infection as an underlying cause6 .

  • Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor complex in the brain, resulting in neural inhibition. A Cochrane review found low-quality evidence suggesting a short-term beneficial effect of flumazenil on hepatic encephalopathy in people with cirrhosis, but no evidence of an effect on all-cause mortality11 .

  • Hepatic encephalopathy may be associated with an impairment of dopaminergic neurotransmission. However, there is insufficient evidence that dopamine agonists are of benefit to patients with acute or chronic hepatic encephalopathy, or fulminant hepatic failure12 .

  • Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids to aromatic amino acids. A Cochrane review found that branched-chain amino acids had a beneficial effect on hepatic encephalopathy but did not find any effect on mortality, quality of life, or nutritional parameters13 .

  • Zinc may be given if there is a deficiency6 .

Hepatic encephalopathy prognosis

The prognosis of hepatic encephalopathy is dependent on the degree of liver failure, comorbidities and the timing of effective treatment, especially of precipitating factors. The development of hepatic encephalopathy in patients with cirrhosis is associated with a worse prognosis and may lead to frequent and severe relapses. Patients with overt hepatic encephalopathy in hospital have a 3.9-fold increased mortality risk14 .


Rifaximin is recommended by the National Institute for Health and Care Excellence (NICE) as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older15 .

Further reading and references

  1. Liu A, Perumpail RB, Kumari R, et al; Advances in cirrhosis: Optimizing the management of hepatic encephalopathy. World J Hepatol. 2015 Dec 18;7(29):2871-9. doi: 10.4254/wjh.v7.i29.2871.
  2. Patidar KR, Bajaj JS; Covert and Overt Hepatic Encephalopathy: Diagnosis and Management. Clin Gastroenterol Hepatol. 2015 Nov;13(12):2048-61. doi: 10.1016/j.cgh.2015.06.039. Epub 2015 Jul 9.
  3. Grover VP, Tognarelli JM, Massie N, et al; The why and wherefore of hepatic encephalopathy. Int J Gen Med. 2015 Dec 16;8:381-90. doi: 10.2147/IJGM.S86854. eCollection 2015.
  4. Leise MD, Poterucha JJ, Kamath PS, et al; Management of hepatic encephalopathy in the hospital. Mayo Clin Proc. 2014 Feb;89(2):241-53. doi: 10.1016/j.mayocp.2013.11.009. Epub 2014 Jan 8.
  5. Mullen KD; Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25 Suppl 1:11-6.
  6. Mandiga P, Foris LA, Bollu PC; Hepatic Encephalopathy
  7. Shawcross D, Jalan R; Dispelling myths in the treatment of hepatic encephalopathy. Lancet. 2005 Jan 29-Feb 4;365(9457):431-3.
  8. Cabral CM, Burns DL; Low-protein diets for hepatic encephalopathy debunked: let them eat steak. Nutr Clin Pract. 2011 Apr;26(2):155-9. doi: 10.1177/0884533611400086.
  9. Heidelbaugh JJ, Sherbondy M; Cirrhosis and chronic liver failure: part II. Complications and treatment. Am Fam Physician. 2006 Sep 1;74(5):767-76.
  10. Zacharias HD, Zacharias AP, Gluud LL, et al; Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis. Cochrane Database Syst Rev. 2019 Jun 17;6:CD012334. doi: 10.1002/14651858.CD012334.pub2.
  11. Goh ET, Andersen ML, Morgan MY, et al; Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy. Cochrane Database Syst Rev. 2017 Aug 10;8:CD002798. doi: 10.1002/14651858.CD002798.pub4.
  12. Junker AE, Als-Nielsen B, Gluud C, et al; Dopamine agents for hepatic encephalopathy. Cochrane Database Syst Rev. 2014 Feb 10;2:CD003047. doi: 10.1002/14651858.CD003047.pub3.
  13. Gluud LL, Dam G, Les I, et al; Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015 Feb 25;2:CD001939. doi: 10.1002/14651858.CD001939.pub2.
  14. Chacko KR, Sigal SH; Update on management of patients with overt hepatic encephalopathy. Hosp Pract (1995). 2013 Aug;41(3):48-59. doi: 10.3810/hp.2013.08.1068.
  15. Rifaximin for preventing episodes of overt hepatic encephalopathy; NICE Technology Appraisal Guidance, March 2015

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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